Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction

Autores
Nolly, Mariela Beatriz; Vargas, Lorena Alejandra; Correa, María Verónica; Lofeudo, Juan Manuel; Pinilla, Oscar Andrés; Vélez Rueda, Jorge Omar; Guerrero-Gimenez, Martin E.; Swenson, Erik R.; Damiani, María T.; Álvarez, Bernardo Víctor
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Myocardial infarction (MI) is one of the leading causes of death worldwide. Prognosis and mortality rate are directly related to infarct size and post-infarction pathological heart remodeling, which can lead to heart failure. Hypoxic MI-affected areas increase the expression of hypoxia-inducible factor (HIF-1), inducing infarct size reduction and improving cardiac function. Hypoxia translocates HIF-1 to the nucleus, activating carbonic anhydrase IX (CAIX) transcription. CAIX regulates myocardial intracellular pH, critical for heart performance. Our objective was to investigate CAIX participation and relation with sodium bicarbonate transporters 1 (NBC1) and HIF-1 in cardiac remodeling after MI. We analyzed this pathway in an "in vivo" rat coronary artery ligation model and isolated cardiomyocytes maintained under hypoxia. Immunohistochemical studies revealed an increase in HIF-1 levels after 2 h of infarction. Similar results were observed in 2-h infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes with a nuclear distribution (confocal microscopy). Immunohistochemical studies showed an increase CAIX in the infarcted area at 2 h, mainly distributed throughout the cell and localized in the plasma membrane at 24 h. Similar results were observed in 2 h in infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes (confocal microscopy). NBC1 expression increased in cardiac tissue after 2 h of infarction (immunoblotting). CAIX and NBC1 interaction increases in cardiac tissue subjected to MI for 2h when CAIX is present (immunoprecipitation). These results suggest that CAIX interacts with NBC1 in our infarct model as a mechanism to prevent acidic damage in hypoxic tissue, making it a promising therapeutic target.
Centro de Investigaciones Cardiovasculares
Comisión de Investigaciones Científicas de la provincia de Buenos Aires
Materia
Ciencias Médicas
CAIX
HIF-1
NBC1
Myocardial infarction
Hypoxia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/144176
Acceder
id SEDICI_cf7aa96a1510beaf5f21afcb30af216b
oai_identifier_str oai:sedici.unlp.edu.ar:10915/144176
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarctionNolly, Mariela BeatrizVargas, Lorena AlejandraCorrea, María VerónicaLofeudo, Juan ManuelPinilla, Oscar AndrésVélez Rueda, Jorge OmarGuerrero-Gimenez, Martin E.Swenson, Erik R.Damiani, María T.Álvarez, Bernardo VíctorCiencias MédicasCAIXHIF-1NBC1Myocardial infarctionHypoxiaMyocardial infarction (MI) is one of the leading causes of death worldwide. Prognosis and mortality rate are directly related to infarct size and post-infarction pathological heart remodeling, which can lead to heart failure. Hypoxic MI-affected areas increase the expression of hypoxia-inducible factor (HIF-1), inducing infarct size reduction and improving cardiac function. Hypoxia translocates HIF-1 to the nucleus, activating carbonic anhydrase IX (CAIX) transcription. CAIX regulates myocardial intracellular pH, critical for heart performance. Our objective was to investigate CAIX participation and relation with sodium bicarbonate transporters 1 (NBC1) and HIF-1 in cardiac remodeling after MI. We analyzed this pathway in an "in vivo" rat coronary artery ligation model and isolated cardiomyocytes maintained under hypoxia. Immunohistochemical studies revealed an increase in HIF-1 levels after 2 h of infarction. Similar results were observed in 2-h infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes with a nuclear distribution (confocal microscopy). Immunohistochemical studies showed an increase CAIX in the infarcted area at 2 h, mainly distributed throughout the cell and localized in the plasma membrane at 24 h. Similar results were observed in 2 h in infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes (confocal microscopy). NBC1 expression increased in cardiac tissue after 2 h of infarction (immunoblotting). CAIX and NBC1 interaction increases in cardiac tissue subjected to MI for 2h when CAIX is present (immunoprecipitation). These results suggest that CAIX interacts with NBC1 in our infarct model as a mechanism to prevent acidic damage in hypoxic tissue, making it a promising therapeutic target.Centro de Investigaciones CardiovascularesComisión de Investigaciones Científicas de la provincia de Buenos Aires2021-07-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1273-1285http://sedici.unlp.edu.ar/handle/10915/144176enginfo:eu-repo/semantics/altIdentifier/issn/1432-2013info:eu-repo/semantics/altIdentifier/issn/0031-6768info:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-021-02592-5info:eu-repo/semantics/altIdentifier/pmid/34231059info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-17T10:15:10Zoai:sedici.unlp.edu.ar:10915/144176Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-17 10:15:10.399SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
title Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
spellingShingle Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
Nolly, Mariela Beatriz
Ciencias Médicas
CAIX
HIF-1
NBC1
Myocardial infarction
Hypoxia
title_short Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
title_full Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
title_fullStr Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
title_full_unstemmed Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
title_sort Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
dc.creator.none.fl_str_mv Nolly, Mariela Beatriz
Vargas, Lorena Alejandra
Correa, María Verónica
Lofeudo, Juan Manuel
Pinilla, Oscar Andrés
Vélez Rueda, Jorge Omar
Guerrero-Gimenez, Martin E.
Swenson, Erik R.
Damiani, María T.
Álvarez, Bernardo Víctor
author Nolly, Mariela Beatriz
author_facet Nolly, Mariela Beatriz
Vargas, Lorena Alejandra
Correa, María Verónica
Lofeudo, Juan Manuel
Pinilla, Oscar Andrés
Vélez Rueda, Jorge Omar
Guerrero-Gimenez, Martin E.
Swenson, Erik R.
Damiani, María T.
Álvarez, Bernardo Víctor
author_role author
author2 Vargas, Lorena Alejandra
Correa, María Verónica
Lofeudo, Juan Manuel
Pinilla, Oscar Andrés
Vélez Rueda, Jorge Omar
Guerrero-Gimenez, Martin E.
Swenson, Erik R.
Damiani, María T.
Álvarez, Bernardo Víctor
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
CAIX
HIF-1
NBC1
Myocardial infarction
Hypoxia
topic Ciencias Médicas
CAIX
HIF-1
NBC1
Myocardial infarction
Hypoxia
dc.description.none.fl_txt_mv Myocardial infarction (MI) is one of the leading causes of death worldwide. Prognosis and mortality rate are directly related to infarct size and post-infarction pathological heart remodeling, which can lead to heart failure. Hypoxic MI-affected areas increase the expression of hypoxia-inducible factor (HIF-1), inducing infarct size reduction and improving cardiac function. Hypoxia translocates HIF-1 to the nucleus, activating carbonic anhydrase IX (CAIX) transcription. CAIX regulates myocardial intracellular pH, critical for heart performance. Our objective was to investigate CAIX participation and relation with sodium bicarbonate transporters 1 (NBC1) and HIF-1 in cardiac remodeling after MI. We analyzed this pathway in an "in vivo" rat coronary artery ligation model and isolated cardiomyocytes maintained under hypoxia. Immunohistochemical studies revealed an increase in HIF-1 levels after 2 h of infarction. Similar results were observed in 2-h infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes with a nuclear distribution (confocal microscopy). Immunohistochemical studies showed an increase CAIX in the infarcted area at 2 h, mainly distributed throughout the cell and localized in the plasma membrane at 24 h. Similar results were observed in 2 h in infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes (confocal microscopy). NBC1 expression increased in cardiac tissue after 2 h of infarction (immunoblotting). CAIX and NBC1 interaction increases in cardiac tissue subjected to MI for 2h when CAIX is present (immunoprecipitation). These results suggest that CAIX interacts with NBC1 in our infarct model as a mechanism to prevent acidic damage in hypoxic tissue, making it a promising therapeutic target.
Centro de Investigaciones Cardiovasculares
Comisión de Investigaciones Científicas de la provincia de Buenos Aires
description Myocardial infarction (MI) is one of the leading causes of death worldwide. Prognosis and mortality rate are directly related to infarct size and post-infarction pathological heart remodeling, which can lead to heart failure. Hypoxic MI-affected areas increase the expression of hypoxia-inducible factor (HIF-1), inducing infarct size reduction and improving cardiac function. Hypoxia translocates HIF-1 to the nucleus, activating carbonic anhydrase IX (CAIX) transcription. CAIX regulates myocardial intracellular pH, critical for heart performance. Our objective was to investigate CAIX participation and relation with sodium bicarbonate transporters 1 (NBC1) and HIF-1 in cardiac remodeling after MI. We analyzed this pathway in an "in vivo" rat coronary artery ligation model and isolated cardiomyocytes maintained under hypoxia. Immunohistochemical studies revealed an increase in HIF-1 levels after 2 h of infarction. Similar results were observed in 2-h infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes with a nuclear distribution (confocal microscopy). Immunohistochemical studies showed an increase CAIX in the infarcted area at 2 h, mainly distributed throughout the cell and localized in the plasma membrane at 24 h. Similar results were observed in 2 h in infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes (confocal microscopy). NBC1 expression increased in cardiac tissue after 2 h of infarction (immunoblotting). CAIX and NBC1 interaction increases in cardiac tissue subjected to MI for 2h when CAIX is present (immunoprecipitation). These results suggest that CAIX interacts with NBC1 in our infarct model as a mechanism to prevent acidic damage in hypoxic tissue, making it a promising therapeutic target.
publishDate 2021
dc.date.none.fl_str_mv 2021-07-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/144176
url http://sedici.unlp.edu.ar/handle/10915/144176
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1432-2013
info:eu-repo/semantics/altIdentifier/issn/0031-6768
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-021-02592-5
info:eu-repo/semantics/altIdentifier/pmid/34231059
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
1273-1285
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.004268

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